Palm oil consumption and its repercussion on endogenous fatty acids distribution.

The consumption of saturated lipids in combination with a sedentary lifestyle increases the risk of obesity and metabolic syndrome. However, the distribution of endogenous fatty acids (FA) after the consumption of saturated lipids and the connection between FA distribution and lipid metabolism-related genes relative expression have not been fully elucidated to date. In this study, we characterized FA profiles in the liver and visceral fats of Sprague Dawley (SD) rats fed with a high-palm-oil diet. The investigation showed that the levels of C16:0 and C18:1 (n-9) increased significantly (P < 0.05) in the liver of the high-palm-oil group (POG), while C16:1 (n-7) and C18:2 (n-6) accumulated markedly (P < 0.05) in the visceral fats of the control group (CN). A correlation analysis indicated a negative correlation between C16:0 and C16:1 (n-7) in the epididymal fat of POG. Our study also demonstrated that the intake of saturated lipids caused changes in lipid metabolism-related gene expression, especially stearoyl-CoA desaturase (SCD), which was upregulated at the third week but was inhibited in the subsequent weeks in the POG liver and perirenal fat. The SCD had a notable positive correlation with C16:1 (n-7) in the POG liver and perirenal fat but a significant negative correlation with C16:0 in the POG epididymal fat. In conclusion, the results of this study indicate that a high-C16:0 diet may result in adaptive SCD expression, and these findings may help to elucidate the effects of dietary fat on lipid metabolism.

Lipid composition modulates the intestine digestion rate and serum lipid status of different edible oils: a combination of in vitro and in vivo studies.

The objective of the present study was to investigate the connections between lipid compositions and the digestion and absorption differences of different lipids. Five typical edible oils (palm oil, PO; leaf lard oil, LO; rapeseed oil, RO; sunflower oil, SO; linseed oil, LINO) were selected to conduct in vitro digestion experiments considering the lipid digestion extent and hydrolysis rate before analyzing the fatty acid composition and TAG profiles using GC and UHPLC-Q-TOF-MS/MS. Meanwhile, the postprandial lipid absorption status after gavage administration was examined in adult male Sprague-Dawley rats with respect to serum lipid profiles. The results showed that the maximum FFA release extent decreased in the order: PO > RO > LINO > SO > LO, and the FFA release apparent constants were PO > SO ≈ RO > LO ≈ LINO. This suggested that the fatty acid species and the location of fatty acids within TAG molecules could significantly affect the lipid digestion fates in the gastrointestinal tract, and short chain saturated fatty acids located at the Sn-1, 3 position could favor the lipid digestion process. PO and LO were both shown to be more likely to affect the serum TG levels and LDL-C : HDL-C ratio compared with RO, SO and LINO. Different fatty acids displayed different correlations with serum lipid profiles when examined by Pearson correlation analysis. This suggested that fatty acid composition and TAG profiles may influence first the digestion rate and then the serum lipid profiles. This further confirmed that lipid composition could modulate the digestion and absorption status under the gastrointestinal conditions. These findings may provide some basic understanding of the connections between lipid composition and their functional difference.

Fatty acid profiles of typical dietary lipids after gastrointestinal digestion and absorbtion: A combination study between in-vitro and in-vivo.

The objective of the present study was to investigate the influences of dietary lipid composition on the gastrointestinal digestion and postprandial serum lipid profiles, and the connections between them. The in-vitro digestion results showed that maximum free fatty acid (FFA) release level of different lipid samples was PO (Palm oil) > RO (Rapeseed oil) > LINO (Linseed oil) > SO (Sunflower oil) > LO (Lard oil), and the first-order kinetics apparent rate constant was PO > SO ≈ RO > LO ≈ LINO, this may probably be ascribed to their specific lipid fatty acid composition and TAG structure. The individual FFA released during 240 min in-vitro digestion time was measured, and it showed that the release rate of short-chain saturated fatty acids (e.g. C16:0 in PO) were higher than the long-chain poly-unsaturated fatty acids (e.g. C18:3n-3 in LINO). Besides, the position of fatty acids within TAG molecules could also impose influences on the lipid hydrolysis process upon pancreas lipase in gastrointestinal tract using in-vitro digestion model. The postprandial serum fatty acid composition of the adult SD male rats were examined within 240 min after oral gavage administration, and the Pearson correlations between lipid fatty acid composition and the serum fatty acid profiles were analyzed. Certain correlations were summarized between lipid compositions (i.e. fatty acid composition and TAG structure), lipid digestion fates and serum fatty acid content in postprandial. The present work may provide some basic understandings of the connections among lipid compositions, lipid gastrointestinal digestion differences and the postprandial serum lipid profiles, and provide useful information about their nutritional and functional evaluation.

Microfluidic whole blood testing of platelet response to pharmacological agents.

Platelets present a number of intracellular and transmembrane targets subject to pharmacological modulation, either for cardiovascular disease reduction or as an unintended drug response. Microfluidic devices allow human blood to clot on a defined surface under controlled hemodynamic and pharmacological conditions. The potencies of a number of antiplatelet and anticancer drugs have been tested with respect to platelet deposition on collagen under flow. Inhibitors of cyclooxygenase-1 (COX-1) reduce platelet deposition, either when added ex vivo to blood or ingested orally by patients prior to testing. Some individuals display a functional "aspirin-insensitivity" in microfluidic assay. When certain nonsteroidal anti-inflammatory drugs (NSAIDs) are taken orally, they block COX-1 acetylation by aspirin with concomitant reduction of aspirin efficacy against platelets in microfluidic assay. Both P2Y1 and P2Y12 inhibitors reduce platelet deposition under flow, as do NO donors and iloprost that target the guanylate cyclase and the prostacyclin receptor, respectively. In a microfluidic assay of 37 kinase inhibitors, dasatinib had potent antiplatelet activity, while bosutinib was less potent. Dasatinib and bosutinib have known profiles against numerous kinases, revealing overlapping and nonoverlapping activities relevant to their unique actions against platelets. Also, dasatinib caused a marked and specific inhibition of GPVI signaling induced by convulxin, consistent with a dasatinib-associated bleeding risk. Microfluidic devices facilitate drug library screening, dose-response testing, and drug-drug interaction studies. Kinase inhibitors developed as anticancer agents may present antiplatelet activities that are detectable by microfluidic assay and potentially linked to bleeding risks.

Detection of platelet sensitivity to inhibitors of COX-1, P2Y1, and P2Y12 using a whole blood microfluidic flow assay.

BACKGROUND: Microfluidic devices recreate the hemodynamic conditions of thrombosis. METHODS: Whole blood inhibited with PPACK was treated ex vivo with inhibitors and perfused over collagen for 300 s (wall shear rate=200 s(-1)) using a microfluidic flow assay. Platelet accumulation was measured in the presence of COX-1 inhibitor (aspirin, ASA), P2Y1 inhibitor (MRS 2179), P2Y12 inhibitor (2MeSAMP) or combined P2Y1 and P2Y12 inhibitors. RESULTS: High dose ASA (500 µM), 2MeSAMP (100 µM), MRS 2179 (10 µM), or combined 2MeSAMP and MRS 2179 decreased total platelet accumulation by 27.5%, 75.6%, 77.7%, and 87.9% (p<0.01), respectively. ASA reduced secondary aggregation rate between 150 and 300 s without effect on primary deposition rate on collagen from 60 to 150 s. In contrast, 2MeSAMP and MRS 2179 acted earlier and reduced primary deposition to collagen between 60 and 105 s and secondary aggregation between 105 and 300 s. R(COX) and R(P2Y) (defined as a ratio of secondary aggregation rate to primary deposition rate) demonstrated 9 of 10 subjects had R(COX)<1 or R(P2Y)<1 following ASA or 2MeSAMP addition, while 6 of 10 subjects had R(P2Y)<1 following MRS 2179 addition. Combined MRS 2179 and 2MeSAMP inhibited primary platelet deposition rate and platelet secondary aggregation beyond that of each individual inhibitor. Receiver-Operator Characteristic area under the curve (AUC) indicated the robustness of R(COX) and R(P2Y) to detect inhibition of secondary platelet aggregation by ASA, 2MeSAMP, and MRS 2179 (AUC of 0.874 0.966, and 0.889, respectively). CONCLUSIONS: Microfluidic devices can detect platelet sensitivity to antiplatelet agents. The R-value can serve as a self-normalized metric of platelet function for a single blood sample.